KLIFS - the structural kinase database

Structure information


PDB:	4OTI
PubMed:	25111382
Release date:	2014-08-27
Resolution:	1.93 Å

Kinase:	PKN1
Family:	PKN
Group:	AGC
Species:	HUMAN

Quality Score:	7.6
Missing Residues:	1
Missing Atoms:	0

DFG conformation:	in
αC-helix conformation:	in
Salt bridge K^III.17 and E^αC.24:	Yes (2.6Å)


ASP rotation (xDFG.81) :	5°
PHE rotation (xDFG.82) :	300°
Activation loop position:	-5.3Å
αC-helix position:	19.5Å

G-rich loop angle:	55.6°
G-rich loop distance:	16.5Å
G-rich loop rotation:	76.3°

Other models from this PDB:

2D & 3D views

Binding pocket waters

The following waters were found in the defined clusters:

I1

H-bond protein

I4

H-bond protein

Binding pocket sequence

Uniprot	AVLGRGHFGKVLLFAIKALSLMCEKRILAAVTPFLVNLFGCCFVMEYSAGGDLMLHIHSFLHEHKIVYRDLKLDNLLLIADFGLC
Structure:	AVLGRGHFGKVLLFAIKALSLMCEKRILAAVTPFLVNLFGCCFVMEYSAGGDLMLHIHSFLHEHKIVYRDLKLDNLLLIADFGL_

Modified residues

Residue 922 (not in pocket)

Phosphorylated serine

Orthosteric ligand

Ligand HET-code: MI1
Ligand Name: 3-{(3R,4R)-4-methyl-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl}-3-oxopropanenitrile

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LABELS
KLIFS residue #
Amino Acid
None
COLORS
Interaction types
KLIFS (all res.)
KLIFS (interacting res.)
None
OTHER
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En/disable resizing interacting res.

This ligand targets the following (sub)pockets:

Main pockets
Front
Gate
Back

Subpockets
FP-I
FP-II
BP-I-A
BP-I-B
BP-II-in
BP-II-A-in
BP-II-B-in
BP-II-out
BP-II-B
BP-III
BP-IV
BP-V

Kinase-ligand interactions

■ Hydrophobic ♦ Aromatic face-to-face ♦ Aromatic face-to-edge ▲ H-bond donor ▲ H-bond acceptor ● Ionic positive ● Ionic negative

I

g.l

II

III

αC

1 A
625

2 V
626

3 L
627

4 G
628

5 R
629

6 G
630

7 H
631

8 F
632

9 G
633

10 K
634

11 V
635

12 L
636

13 L
637

14 F
647

15 A
648

16 I
649

17 K
650

18 A
651

19 L
652

20 S
665

■

■▲

■

αC

b.l

IV

21 L
666

22 M
667

23 C
668

24 E
669

25 K
670

26 R
671

27 I
672

28 L
673

29 A
674

30 A
675

31 V
676

32 T
677

33 P
682

34 F
683

35 L
684

36 V
685

37 N
686

38 L
687

39 F
688

40 G
689

■

IV

V

GK

hinge

linker

αD

αE

41 C
690

42 C
698

43 F
699

44 V
700

45 M
701

46 E
702

47 Y
703

48 S
704

49 A
705

50 G
706

51 G
707

52 D
708

53 L
709

54 M
710

55 L
711

56 H
712

57 I
713

58 H
714

59 S
715

60 F
736

■

▲

■♦

■▲

αE

VI

c.l

VII

VIII

x

61 L
737

62 H
738

63 E
739

64 H
740

65 K
741

66 I
742

67 V
743

68 Y
744

69 R
745

70 D
746

71 L
747

72 K
748

73 L
749

74 D
750

75 N
751

76 L
752

77 L
753

78 L
754

79 I
762

80 A
763

■

DFG

a.l

81 D
764

82 F
765

83 G
766

84 L
767

85 _
_

■

Interaction pattern search

Search KLIFS for kinase-ligand complexes with similar interaction patterns:

Binding affinities

ChEMBL ID:CHEMBL221959
Bioaffinities: 486 records for 42 kinase(s)

Species	Kinase (ChEMBL naming)	Median	Min	Max	Type	Records
Homo sapiens	BMP-2-inducible protein kinase	5.2	5.2	5.2	pKd	1
Homo sapiens	CaM kinase I alpha	5.3	5.3	5.9	pKd	3
Homo sapiens	CaM kinase I delta	5.8	5.8	5.8	pKd	1
Homo sapiens	CaM kinase II alpha	5.5	5.5	5.5	pKd	1
Homo sapiens	CaM kinase II delta	5.6	5.6	5.6	pKd	1
Homo sapiens	Dual specificity mitogen-activated protein kinase kinase 1	6.4	6.4	6.4	pKd	1
Homo sapiens	G protein-coupled receptor kinase 7	5.4	5.4	5.4	pKd	1
Homo sapiens	Leucine-rich repeat serine/threonine-protein kinase 2	5.9	5.9	6.3	pKd	2
Homo sapiens	MAP kinase signal-integrating kinase 2	5.8	5.8	5.8	pKd	1
Homo sapiens	MAP/microtubule affinity-regulating kinase 2	5.2	5.2	5.2	pKd	1
Homo sapiens	Mitogen-activated protein kinase kinase kinase kinase 2	5.3	5.3	5.3	pKd	1
Homo sapiens	Myotonin-protein kinase	5.9	5.9	5.9	pKd	1
Homo sapiens	Non-receptor tyrosine-protein kinase TNK1	6.2	5.8	6.9	pKd	4
Homo sapiens	NUAK family SNF1-like kinase 2	6.4	6.4	6.6	pKd	3
Homo sapiens	Protein kinase C alpha	4.6	4.6	4.6	pKd	1
Homo sapiens	Protein kinase C delta	5	5	5.7	pKd	2
Homo sapiens	Protein kinase N1	6.7	6.7	7.2	pKd	4
Homo sapiens	Protein kinase N2	5.9	5.9	5.9	pKd	1
Homo sapiens	Rho-associated protein kinase 1	5.6	5.6	6.3	pKd	2
Homo sapiens	Rho-associated protein kinase 2	5.5	5.5	5.5	pIC50	2
Homo sapiens	Rho-associated protein kinase 2	5.5	5.5	6.4	pKd	2
Homo sapiens	Ribosomal protein S6 kinase alpha 1	5.9	5.9	5.9	pKd	2
Homo sapiens	Ribosomal protein S6 kinase alpha 2	5.9	5.9	6.2	pKd	6
Homo sapiens	Ribosomal protein S6 kinase alpha 6	5.9	5.9	6.3	pKd	6
Homo sapiens	Serine/threonine-protein kinase Aurora-B	6.3	6.3	6.3	pKd	1
Homo sapiens	Serine/threonine-protein kinase c-TAK1	5	5	5	pKd	1
Homo sapiens	Serine/threonine-protein kinase DCLK1	5.2	5.2	5.2	pKd	1
Homo sapiens	Serine/threonine-protein kinase DCLK3	8.4	7.9	8.4	pKd	3
Homo sapiens	Serine/threonine-protein kinase MST2	5.4	5.4	5.4	pKd	2
Mycobacterium tuberculosis	Serine/threonine-protein kinase pknB	5.7	5.7	5.7	pKd	1
Homo sapiens	Serine/threonine-protein kinase ULK3	5.2	5.2	5.2	pKd	1
Homo sapiens	Tyrosine kinase non-receptor protein 2	6	6	6	pKd	1
Homo sapiens	Tyrosine-protein kinase ABL	5.4	5.2	5.7	pKd	3
Homo sapiens	Tyrosine-protein kinase FYN	6	6	6	pKd	1
Homo sapiens	Tyrosine-protein kinase JAK1	7.3	7.3	7.4	pEC50	10
Homo sapiens	Tyrosine-protein kinase JAK1	8.5	6.9	9.3	pIC50	78
Homo sapiens	Tyrosine-protein kinase JAK1	8.8	8.8	8.8	pKd	4
Homo sapiens	Tyrosine-protein kinase JAK1	9.2	9.2	9.2	pKi	8
Homo sapiens	Tyrosine-protein kinase JAK2	7	6.7	7	pEC50	8
Homo sapiens	Tyrosine-protein kinase JAK2	7.8	5.3	9.3	pIC50	120
Homo sapiens	Tyrosine-protein kinase JAK2	8.3	8.3	9.2	pKd	8
Homo sapiens	Tyrosine-protein kinase JAK2	9.2	9	9.2	pKi	8
Mus musculus	Tyrosine-protein kinase JAK2	5.7	5.7	5.7	pIC50	1
Rattus norvegicus	Tyrosine-protein kinase JAK2	5.3	5.3	5.7	pIC50	4
Homo sapiens	Tyrosine-protein kinase JAK3	8.7	5.9	9.6	pIC50	86
Homo sapiens	Tyrosine-protein kinase JAK3	8.7	8.7	9.8	pKd	8
Homo sapiens	Tyrosine-protein kinase JAK3	9.4	9	9.6	pKi	10
Mus musculus	Tyrosine-protein kinase JAK3	6.8	6.8	7.3	pIC50	4
Homo sapiens	Tyrosine-protein kinase LCK	5.4	5.4	6.5	pIC50	3
Homo sapiens	Tyrosine-protein kinase LCK	5.8	5.8	6.3	pKd	2
Homo sapiens	Tyrosine-protein kinase receptor RET	5.5	5.5	5.5	pKd	1
Homo sapiens	Tyrosine-protein kinase TYK2	6.2	6.2	6.2	pEC50	4
Homo sapiens	Tyrosine-protein kinase TYK2	7.5	5.9	8.4	pIC50	38
Homo sapiens	Tyrosine-protein kinase TYK2	6.2	6.2	8.3	pKd	8
Homo sapiens	Tyrosine-protein kinase TYK2	8.1	8.1	8.4	pKi	8

4OTI - chain A (model A) | Protein kinase N1